Cancer Following Bone Marrow Transplantation 24,011 patients worldwide, treated with allogeneic bone marrow transplants were evaluated for increased risk of all cancer related to the late effects of total-body medical irradiation (8-15 Gy), and severe immunosuppression. Treatments resulting in severe immune dysfunction, were linked to high risks of post-transplant lymphoproliferative disorders. Treatments containing total body irradiation were associated with increased risks of solid tumors, with new findings showing an increased risk of breast cancer among long-term survivors. Cancer Mortality among Women Treated with Radiotherapy for Benign Gynecologic Disease Cancer mortality following radiation treatment for benign gynecologic disease in a cohort of nearly 15,000 women with individual dose data is being updated to evaluate solid tumor and leukemia risk. Cancer Mortality and Incidence Risks in Patients with Scoliosis A multi-center retrospective cohort study of female scoliosis patients monitored with diagnostic x-rays, found that mortality from breast cancer was significantly elevated, whereas, death rates from several other cancers were below expectation. In particular lung, cervical, and liver. Cancer Risks following Use of Diagnostic and Therapeutic I-131 for Hyperthyroidism REB is evaluating the risk of cancer following diagnostic and therapeutic Iodine-131 in several study populations both in U.S. and internationally. Cancer mortality is being updated for hyperthyroid patients treated with I-131, compared to hyperthyroid patients not treated with radio-iodine.Cancer Risks from CT scan Use in the US We are estimating the potential radiation-related cancer risks that may be related to current levels of CT use in adults, and also conducting radiation risk-benefit analyses for CT screening examinations. Cancer Risk in Peptic Ulcer Patients A significantly increased risk of dying from diabetes following high-dose abdominal radiation 15 years and later was observed in a cohort of 2000 irradiated peptic ulcer patients compared to 2000 peptic ulcer patients treated by other means. Dose Comparison (LEE) Radiation doses to the breast of Hodgkin lymphoma patients estimated using stylized phantoms is being compared to dose values obtained using Monte Carlo-based methods using the adult female hybrid phantom to evaluate the reliability of the hybrid phantom. Early Life Radiation and Risk of Child Cancer Studying radiation exposure during early life is of particular importance, given that many tissues are more susceptible to radiation effects in utero and at younger age of exposure. We are currently evaluating in utero and post-natal radiation exposure and the risk of cancer in a population-based case-control study of childhood cancer in the UK. Interventional Fluoroscopy Fluoroscopically-guided radiation procedures can result in high radiation exposure to both the physician and patient. A cohort of physicians who perform interventional radiation procedures, radiologists and a comparison group has been assembled to estimate the risk of dying from cancer especially brain and leukemia. Analyses are in progress. Molecular and Histopathologic Clues to the Understanding of Thyroid Cancer Incidence Thyroid cancer incidence has increased significantly over the last few decades. We are evaluating whether molecular alterations and histopathology of papillary carcinoma have changed over the last three decades, using thyroid tumor tissue collected from three US hospitals. Pediatric CT Scans REB initiated an international cohort study of over 200,000 children to evaluate the potential risk of cancer associated with radiation exposure from pediatric CT scans. A comprehensive organ CT dose database for a total of 30 organs and tissues is being developed in support of a study of pediatric cancer risk and CT exposure. Pooled Analysis of Radiation-Related Thyroid Cancer To improve our understanding of the etiology of thyroid cancer, REB scientists have set up an international consortium to study radiogenic thyroid cancer in children and adults. Proton IMRT Proton and IMRT have the potential to deliver maximal doses to the tumor while minimizing dose to the surrounding tissues which may cause second cancers. An international feasibility study to evaluate the risk of second cancers from this treatment has been initiated. Radiation Dose-Response and Second Primary Cancers of the Stomach, Pancreas and Esophagus An international study of second primary gastrointestinal (GI) (stomach, pancreatic, and esophageal) cancers is being conducted among survivors of Hodgkin lymphoma (HL), testis, breast and cervical cancer to provide new data on radiation dose and subsequent risk of GI cancer. Available biologic samples will be analyzed to identify patterns of genomic aberrations in radiotherapy-induced cancers. Findings to date have demonstrated a dose-related increased risk of esophageal cancer following breast cancer. Analyses of GI malignancy risk after HL and testis and cervical cancers are in progress. Risk Factors for Second Cancers in the Cohort Consortium The feasibility of studying second cancers in the NCI Cohort Consortium is being assessed. Second Cancer Risks following Retinoblastoma A cohort of 1,850 Retinoblastoma continues to be monitored for second primary cancers, primarily of the bone, soft tissue, and melanoma. An increased risk for uterine leiomyosarcoma 30 years and later in these patients was observed. Second Cancers after Breast Cancer in three Cohorts (Kaiser, Million women study and AARP) The etiology of contralateral breast is probably related to treatment, genetic and lifestyle risk factors. We are exploring the feasibility of studying treatment and modifiable lifestyle risk factors for contralateral breast cancer in three different cohorts. Secondary Cancers of the Brain, Breast, and Thyroid among Childhood Cancer Survivors In a cohort of 14,000 5-year survivors of childhood cancer we performed nested case-control studies of second primary cancers of the breast, thyroid gland, salivary gland, bone, soft tissue and skin to evaluate the relationship between radiation and chemotherapy and risk of these cancers. A novel finding was that thyroid cancer risk was related to prior treatment with alkylating agents among patients exposed to radiation less than 20 Gy to the thyroid. Serum Markers of immunity and Risk of Brain Tumors Evidence that a history of allergy and/or autoimmune diseases is associated with a reduced risk of gliomas in adults will be followed up in a case-control study of adult gliomas nested within 7 million U.S. military personnel with pre-diagnostic serum samples. We will quantify the dose-response relationship between risk of gliomas and levels of selected cytokines/growth factors and immune-related disorders in the subjects.